Despite the significant decline in caries prevalence, caries remain one of the most prevalent diseases of our times. However, we have only limited understanding of the natural history of the disease and are unable to accurately and objectively identify early lesions and/or lesions that are actively progressing. The use of innovative visual caries criteria in combination with available instrumental imaging technologies capable of quantifying changes in the severity of the lesions may permit smaller and shorter clinical trials. Previous studies have indicated that Quantitative Light Induced Fluorescence (QLF), an imaging technique, has high sensitivity but low specificity for detection of the early stages of caries lesions while a new visual criteria, the International Caries Detection and Assessment System (ICDAS) has high specificity. To achieve high sensitivity without loss of specificity we propose to combine the QLF exam with the ICDAS criteria. It is anticipated that once a certain value for the ICDAS/QLF score and/or QLF parameters is reached, it will be a reliable surrogate for traditional cavitation measures. For detection of approximal lesions a new infrared fluorescence device, DIAGNOdent pen, redesigned for the detection of approximal caries will be evaluated in combination with ICDAS. The primary goal of this investigation is to determine, using a prospective longitudinal study design, if a combination of ICDAS and QLF, can detect carious lesions at an early stage and use them as surrogates for traditional cavitation measures. To enable this research we propose to enroll children at high-risk of future caries and follow them for 4 years using a clinical end point (cavitation). The Specific Aims of this study are to: 1) Establish, the feasibility of using early non-cavitated caries lesions as surrogate for the true clinical endpoint, cavitated lesions, by following the natural history of dental caries in a group of high-risk children over a four year period; 2) Determine if early dental caries lesions as identified by a combination of visual criteria (ICDAS) and QLF exam can be used as a surrogate for cavitated lesions; and 3) To determine if approximal early lesions as identified by a combination of ICDAS and a modified DIAGNOdent pen can be used as a surrogate for radiographically evident lesions. The successful validation of this early caries detection approach will provide the tools necessary for clinicians and researchers to advance the field and reduce the burden of the most common disease facing mankind. [unreadable] [unreadable] [unreadable]